GALC

Summary: The ancestral galactosylceramidase assertion is consistent with the exact human target and direct human biochemistry.

Reason: The retained PTHR15172 tree places human P54803 at AN16/PTN002495607 below the actual AN0/PTN001032282 assertion, with an exact 685-residue target alignment and no retained negative assertion. Human purification and expression evidence corroborate the activity. The incoming donor list predates the retained addition of a zebrafish donor; both versions are preserved. Target self-donation reflects experimental grounding and is not circular evidence.

Summary: Human GALC cDNA expression establishes the core enzyme activity.

Reason: The authentic PMID:8281145 abstract describes cloning human GALC cDNA and increased GALC activity after expression in COS-1 cells. Cat RNA was an intermediate used to obtain a screening probe, not the identity of the expressed enzyme. The paper describes a 669-residue coding region; that historical construct is not silently equated with the current 685-residue displayed sequence. Full original Methods were not recovered, but the reported positive expression result and independent purified human enzyme evidence support the activity. This original unextended context remains distinct from the separately assigned substrate/product context.

Summary: Purification and characterization of human GALC directly support its defining catalytic activity.

Reason: The authentic PMID:8399327 abstract reports purification of human urine GALC, enrichment of activity and largely enzyme-specific purified fractions, with related material from brain and placenta. Detailed original assay Methods were not inspected. Independently, the curated UniProt BIOPHYSICOCHEMICAL PROPERTIES section attributes a Km of 10 micromolar for N-acyl-beta-D-galactosylsphingosine and an optimum pH of 4.0–4.4 to this PMID. These are usable curated evidence, not newly read primary assay details. The N-acyl substrate in the Km statement is distinguished from the separate psychosine reaction. Molecular-weight bands are not equated with natural splice products.

Summary: The combined electronic sources correctly identify galactosylceramidase activity.

Reason: The literal combined ARBA, ortholog, InterPro, RHEA and EC sources agree with the experimentally demonstrated human enzyme function. The specific activity is supported independently by purification of human GALC and expression of its cDNA. The combined source list is one electronic inference, not six independent experiments; complete individual ARBA rule execution is not claimed.

Summary: The mouse-ortholog inference identifies the defining galactosylceramidase activity.

Reason: The literal source P54818 is mouse Galc. Human GALC purification and cDNA-expression studies independently establish the same enzyme activity, so the target claim does not depend only on ortholog similarity. GALC cleaves the glycosidic linkage joining galactose to ceramide; the inherited UniProt ester-bond wording is not adopted as chemistry. No activity equivalence is inferred for every alternative product.

Summary: The Reactome galactosylceramide-hydrolysis reaction supports the core GALC activity.

Reason: The curated reaction attributes galactosylceramide hydrolysis to GALC, consistent with direct human purification and cDNA-expression evidence. The annotation concerns the enzyme activity, not automatic endorsement of every small-molecule field in the pathway model. The independently checked model participants and any source chemistry discrepancy are documented separately; source records remain immutable. Specifically, reaction output 1605745 resolves to CHEBI:4167 D-glucopyranose, whereas the same catalyst definition specifies D-galactose. The correct GALC activity and the original galactose output context are retained.

Summary: The ancestral lysosome annotation correctly describes GALC's core organelle location.

Reason: The retained lysosome IBD at AN0/PTN001032282 lies on the exact human target path, with no retained negative assertion. Its later donor set adds a zebrafish source without changing the literal older incoming record. Independent GALC enzyme biology and the verified human reaction support lysosomal localization. The root-organelle claim remains informative and is retained as ACCEPT under the organelle policy. More precise lumen evidence is represented by the existing lumen annotations and the endolysosome-lumen core; it does not invalidate or replace this ancestral lysosome assertion.

Summary: The UniProt lysosome-location mapping correctly identifies GALC's core organelle.

Reason: The original SL-0158 mapping agrees with the established lysosomal enzyme biology, soluble hydrolase mechanism and verified GALC reaction. The root-organelle policy retains this informative lysosome claim as ACCEPT. Existing lumen annotations and the endolysosome-lumen core express the supported subcompartment separately; the part_of relation is not a reason to replace the lysosome annotation.

Summary: The literature supports lysosomal localization as part of GALC's core biology.

Reason: The genuine PMID:7601472 abstract describes GALC as catalyzing lysosomal hydrolysis of specific galactolipids. Its main new subject is human gene organization, so the location statement is background traceable evidence rather than a newly inspected localization assay. Independent enzyme biology and the verified human GALC reaction support the lysosome claim. Retain this informative organelle annotation as ACCEPT; the existing lumen annotations and precise core location capture the subcompartment without replacing the literature's organelle-level assertion.

Summary: The ancestral catabolic-process assignment follows the actual target lineage and the conserved catalytic role.

Reason: The literal GO:0006683 IBD is placed at AN0/PTN001032282, ancestral to the exact human P54803 target in the retained PTHR15172 tree. The incoming and retained donor sets agree for this process. Human experimental grounding legitimately appears among the descendant sources, and the short donor list is not evidence against the placement. GALC executes the galactosylceramide-cleavage step directly.

Summary: The cited review describes the correct GALC catabolic reaction, with independent primary support.

Reason: PMID:15657896 is a review whose authentic abstract explicitly assigns conversion of galactosylcerebroside to ceramide to GALC. It is not described here as a newly inspected primary activity assay, and the original IDA evidence code is preserved as source provenance. Independent human purification and expression studies establish the same core process. The cancer-context discussion does not justify additional apoptosis, adhesion or migration annotations.

Summary: Human GALC biochemical characterization supports galactosylceramide catabolism.

Reason: The purified human enzyme is the galactosylceramidase that performs this catabolic step. PMID:8399327 reports enrichment and characterization of GALC activity, and the independent cDNA study identifies the corresponding human enzyme. Full original assay Methods are not claimed read; the correct experimentally curated process is retained without inventing kinetic measurements or a splice-product assignment.

Summary: The InterPro inference captures the galactosylceramide breakdown step performed by GALC.

Reason: The current original reference is GO_REF:0000002 with IPR001286, rather than the older combined-reference record. GALC itself performs the hydrolytic conversion of galactosylceramide, so participation follows from its catalytic role rather than a downstream disease phenotype. Human biochemical and expression evidence support this specific catabolic process.

Summary: The mouse-ortholog transfer agrees with human GALC-mediated galactosylceramide catabolism.

Reason: The literal P54818 source is the mouse GALC ortholog. The human enzyme directly hydrolyzes galactosylceramide, and human cloning and purification studies corroborate the transferred process. This is execution of a catabolic step, not merely a requirement for myelin integrity or a consequence of substrate accumulation.

Summary: The broad sphingolipid-catabolism assertion preserves the experimentally curated breadth of GALC substrates.

Reason: GALC hydrolyzes both galactosylceramide and galactosylsphingosine (psychosine). The unchanged UniProt catalytic record separately curates the latter reaction as RHEA:43908 with PMID:8399327, so replacing this process by galactosylceramide catabolism would lose supported substrate breadth. Production GO-CAM gomodel:696022cd00002259, activity 69729a3800003499, places human GALC activity GO:0004336 in endolysosome lumen and in sphingolipid catabolism with PMID:8281145. The model is a deliberate pathway context; its breadth alone would not prohibit a well-supported refinement, but the independently curated second substrate supplies the biological reason to retain this original broad claim. The exact psychosine reaction is recorded once in the UniProt reference finding and supports this substrate-breadth assessment.

Summary: Endolysosome-lumen activity is a biologically supported curator inference for this acid hydrolase.

Reason: The original IC assertion explicitly derives from galactosylceramidase activity. PMID:27498570 assays cathepsins and acid phosphatase in mammalian cells and identifies hydrolase-active endolysosomes; it does not directly image GALC. The inference is consistent with GALC's soluble acidic-compartment lipid hydrolysis and the GALC-SapA biochemical study. This is part of the core catalytic setting, while the evidence remains an inference rather than a human GALC localization experiment. It does not imply absence of GALC protein from inactive storage lysosomes.

Summary: The GALC-SapA study supports the inferred endolysosomal setting of GALC catalysis.

Reason: Selected original Results and Methods show pH-dependent GALC-SapA association and a murine complex architecture that presents lipid substrate toward the GALC active site. The acidic setting is consistent with late endosomal/lysosomal activity; this remains an IC location inference, not direct human GALC microscopy. The principal structure and interface assays use mouse proteins, with a limited separate human pull-down comparison. The lipid-substrate placement is modeled rather than a resolved substrate-bound complex. The inferred compartment is part of the core enzyme setting, so lower directness of evidence alone does not make it non-core.

Summary: The GALC reaction places the soluble enzyme in lysosomal lumen.

Reason: The Reactome catalyst/entity chain identifies human GALC in the lysosomal lumen. This agrees with the enzyme's role in acidic-compartment galactolipid hydrolysis and the GALC-SapA substrate-presentation mechanism. The model supplies traceable compartment membership, not a new human imaging assay or proof of every natural product's localization. A small-molecule output discrepancy in the same model does not negate the independently supported enzyme identity and compartment.

Summary: The broad glycosphingolipid-catabolism assertion preserves the experimentally curated breadth of GALC substrates.

Reason: Reactome R-HSA-9840310 includes the GALC GalCer-hydrolysis reaction R-HSA-1606564 through its explicit P54803 catalyst; the retained output-label discrepancy does not alter the target enzyme identity or this pathway role. Independent curated human UniProt chemistry also supports psychosine hydrolysis (RHEA:43908, PMID:8399327). Both substrates are glycosphingolipids, so narrowing this original pathway claim to GalCer catabolism would lose supported substrate breadth. The exact second reaction is recorded once in the UniProt reference finding cited here.

Summary: The separately assigned activity context records galactosylceramide hydrolysis to galactose and ceramide.

Reason: The original substrate/product conjunction specifies beta-galactosylceramide input and D-galactose plus N-acylsphingosine outputs, matching GALC glycosidic hydrolysis. Human expression and purification reports support the enzyme activity. All three extension atoms are retained together; the independently assigned unextended activity context remains separate.